PROJECT SUMMARY ? CANCER STEM CELLS PROGRAM The Cancer Stem Cells (CSC) Program is based on two pivotal findings made by program members: 1) only a small percentage of cells in tumors, the cancer stem or initiating cells, drive the growth and metastatic capability of tumors. These cells must be eliminated to achieve a complete therapeutic response; and 2) cancers frequently arise as the consequence of changes in self-renewal pathways, such as the Wnt and the Hedgehog signaling cascades. The CSC Program postulates that self-renewal is a critical function of both cancer stem cells and their normal counterparts and that self-renewal pathways may be co-opted in the process of oncogenesis to support tumor growth. Based on these concepts, the overall goal of the Cancer Stem Cells Program is to identify and characterize self-renewal pathways in model systems, normal tissues, and solid tumors. These efforts require the strong integration of basic research with preclinical studies within the program, as well as collaboration with clinical investigators in other programs. Co-led by Michael Clarke, MD and Roel Nusse, PhD, the 20 members represent three schools (the School of Medicine, the School of Humanities & Sciences and the School of Engineering) and 12 departments. The research activities of the 20 investigators are supported by 41 peer-reviewed, investigator-initiated grants (R01s and others). Peer-reviewed funding is a total of $18.3 million in total costs/year of which $3.3 million is from the NCI, $7.4 million from other NIH sources, and $7.7 million from other peer-reviewed support. Since 2009, program investigators have published over 300 manuscripts relevant to cancer stem cell biology in peer-reviewed journals, of which 19% are intra-programmatic and 42% inter-programmatic, as well as numerous externally collaborative manuscripts. The SCI will continue to be invaluable in seeding innovative projects and assisting with the translation of the basic science findings from this program into new clinical approaches for the diagnosis and treatment of patients with cancer.